The object of the program project is an integrated multidisciplinary approach to rational drug design. In particular, exhaustive enumeration of orientations of functional groups for a series of active compounds will be examined for an indication of the pharmacophore. The introduction of conformational restraints will help ascertain the receptor-bound conformation of angiotensin II, thyroliberin and enkephalin. These restraints will be determined prior to synthesis by calculation of allowed conformations. A core facility consisting of computation equipment for scanning conformational space, input, analysis and display of output and a retrievable library of structure-activity data will be developed to assist in drug design. The facility will also serve to develop algorithms for more efficient determination of the pharmacophore as well as exploitation of the pharmacophore once defined. This approach to rational drug design will be applied to the following systems: dopamine and neuroleptics; the peptides previously mentioned; and steroid-transforming enzymes.